Eric Leuthardt, M.D., a neurosurgeon and Professor of Neurosurgery and Biomedical Engineering at Washington University School of Medicine in St. Louis, talks about the new laser surgery that is used to treat aggressive brain cancer.
Interview conducted by Ivanhoe Broadcast News in April 2016.
Glioblastoma; what is it and how difficult is it traditionally to treat?
Dr. Leuthardt: Glioblastoma is a very malignant type of brain tumor and there are a number of different variants of that. But basically it’s a tumor that comes from one of the cells in the brain and proliferates rapidly and it can be a very life threatening problem.
How common is it?
Dr. Leuthardt: They are relatively uncommon when we take the general population, but of brain tumors there are around forty to fifty percent of tumors that come from the brain.
What are the treatment options?
Dr. Leuthardt: Historically, the treatment options have been to take it out with surgery and you combine that afterwards with radiation chemotherapy. One of the things that have been emerging over the last several years is rather than standard open surgery now what we can do is we can insert a laser probe in to the brain where we heat and kill that tumor from the inside out through a very small incision.
Tell me a little bit about that, can you describe how you go about that procedure?
Dr. Leuthardt: Sure. It’s actually a pretty amazing procedure but it really combines a number of cutting-edge technologies. Number one it involves a small laser probe that’s robotically controlled and the entire surgery is done in an intraoperative MRI scan. When you really just think about the procedure, what it is it’s a small incision probably about the length of my fingernail in the scalp, a small hole in the skull about the width of a pencil. Then this laser probe gets very precisely placed in to the center of the tumor. You can almost think of it as like putting a toothpick in to an olive if you will. That laser probe is then controlled robotically so it can be moved back and forth or rotated remotely. Once the patient has the probe in their tumor they then go in to an MRI scanner and that MRI is critical so you can monitor and very precisely determine both the heat and the position of that probe. A surgeon is outside of the MRI scanner controlling it with a computer interface and we then control and heat and kill that tumor; it’s almost like playing a video game. At the end of it, the patient has a small incision on their head and usually we close it with only one or two stitches. They’ll often go home the next day after surgery.
How important is it when you’re dealing with the brain to be precise, you have no margin for error?
Dr. Leuthardt: Sure. Brain surgery requires precision at many levels. One is you want to kill the tumor and nothing but the tumor because obviously with a number of these tumors that are considered quote unquote, inoperable, the reason they’re inoperable is because they are surrounded by critical structures. If you try to go in to do classic surgical techniques when you open a hole in the skull and go through the brain then you could injure a number of critical nerve tracks that control motor function, speech function or visual function. You have to be precise on that level meaning you want to preserve the tissue around it but also it’s precise in how you get there. Meaning there’s a number of layers of brain function and when you plan your trajectory or when you’re planning how you go in to the brain it’s not just where you are at the end its how you get there. There are a lot of things that you have to avoid along the way.
In terms of recurrence with this particular cancer, do a lot of these tumors come back?
Dr. Leuthardt: They do. These malignant brain tumors do come back. Again, there are a number of different variants of these and they come back depending on the type of variant, can come back at different time scales.
In doing this laser surgery you found something else?
Dr. Leuthardt: That’s right. Number one is the goal of the laser surgery originally was a technical term called cytoreduction. We want to reduce the total tumor burden on the brain. We want to kill as many of the tumor cells as possible. One of the things that we saw after surgery is that there is this unusual effect that we saw, this ring of new enhancement. When you’re trying to define where that tumor is you give them an injection with special dye that you can see on the MRI. We saw a new ring of this dye around where we treated. That’s pretty characteristic that you’ve broken down the blood brain barrier. But to really prove that and to prove the duration we really did an extensive study on a number of patients where we got additional advance types of imaging. We watch the rate at which the dye moves through the brain as well as markers where it can actually see different types of proteins in the blood that are indicative or tell you that the blood brain barrier has been broken down. We were able to discover that we had broken down the blood brain barrier for four to six weeks in our patients after once they had this laser surgery, which is quite different from other surgeries.
When you’re talking about the blood brain barrier what is this?
Dr. Leuthardt: The blood brain barrier is evolution which has created our brain to really resist the ability of toxins to get in to it. The brain is very sensitive so it really only wants oxygen and glucose and a few other things and nothing else. The blood brain barrier is this lining along the vessels that supply blood to our brain to prevent anything else but blood and oxygen from getting in. While that protects you even if you get an infection, it protects you from a number of toxins that could be in your blood. It actually works against you when you’re trying to get chemotherapy to treat the tumor in the brain because it’s really preventing a lot of these chemicals from getting in the brain that could be helpful in killing the tumor. This has always been a really big challenge, is how you get the necessary drugs, medications, various chemotherapeutic agents to treat the tumor when the blood brain barrier is there. By breaking down the blood brain barrier we now have a window or an opportunity to give new type of therapies that would otherwise not get there.
Can you talk a little bit about Campbell?
Dr. Leuthardt: The name of Campbell’s tumor is a mouthful but it’s an anaplastic oligodendraoglioma. It’s considered a higher grade, it is a malignant brain tumor and when we first met him a couple of years ago these are often considered inoperable tumors. We talked about the option of doing laser therapy and he agreed and I think he’s done very well since that time. He has had no neurologic dysfunction, the tumor has been completely treated, he responded very well to therapy after that and he has got no evidence at this time of any recurrence.
What’s his prognosis?
Dr. Leuthardt: Anaplastic aldengendra gleomias usually the time of recurrence is usually around three to five years.
He could still be facing a bit of a mountain?
Dr. Leuthardt: That’s right. But his tumor will come back sometime.
Once you’ve had the laser surgery can it be repeated?
Dr. Leuthardt: Absolutely. There are several patients who got their tumor treated but it came back and we can always do it again.
In terms of implications for this laser surgery and being able to cross the barrier to deliver chemotherapy, what are the implications?
Dr. Leuthardt: Opening that window, it suddenly gives us a new opportunity to do a number of different therapies that would otherwise not be possible. One, is that there’s a number of different chemotherapies that we use in the rest of our body that can treat cancers without the blood brain barrier that have been shown to be effective. We can start to bring those and we have a clinical trial for that right now. This drug which is called doxorubicin is very toxic to cancer cells but typically does not penetrate the blood brain barrier. One can also envision a very directed therapy meaning that if we treat this tumor we also get a piece of it so we can know its genetic profile. We can then start to think about targeted therapies based on the tumor’s molecular and genetic profile which again those may be specific agents that don’t typically get through the blood brain barrier. Finally a really big and emerging field in treating malignant brain tumors is immunotherapy, this idea that you can train your immune system to fight the cancer for you. If you break down the blood brain barrier, it’s a two way street so that not only do you allow things to get in to the brain but also because the tumors proteins and things that could alert the immune system that the tumor is there gets in to the bloodstream. That could potentially enhance any immunotherapy in the future.
In terms of the trial that you talked about can you give me some specifics, how many patients?
Dr. Leuthardt: Yes. I think a total of Phase II, a total of forty patients are being recruited. This is where we combine laser therapy with a drug called doxorubicin. The patients are either getting the chemotherapy early or late when the window is open or afterward to see if there is a difference of how they respond when the blood brain barrier is open.
Is there anything I didn’t ask you that you want people to know?
Dr. Leuthardt: I think we’ve got it covered. One thing I should say is that the work that we’ve done in proving that we could open the blood brain barrier is really a collaborative effort. I think that it really required combined expertise between myself, a neurosurgeon performing the laser surgery, oncology with David Tran and advanced imaging with Josh Shisamony. I think it was that team was really critical to proving some of these findings.
How long is the trial?
Dr. Leuthardt: It’s a six month trial.
Will it go to Phase III?
Dr. Leuthardt: It depends on the results. The preliminary findings are looking good.
Would you expand the numbers with that?
Dr. Leuthardt: Absolutely, it would be a multi institutional trail.
Glioblastoma, does it generally hit all ages?
Dr. Leuthardt: It tends to be older years and I think the mean age is around early sixties.
Is Cam’s type unusual as a thirty six year old?
Dr. Leuthardt: It’s a bell shaped distribution that while you typically see it in older people you can see it in young people as young as twenty one, twenty two unfortunately.
END OF INTERVIEW
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